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Oncotarget | Preclinical evaluation of a nanoformulated antihelminthic, niclosamide, in... - 0 views

www.oncotarget.com/index.php Niclosamide cancer ovarian cancer
shared by Nathan Goodyear on 16 Apr 18 - No Cached
  • Ovarian cancer is the most lethal gynecologic malignancy in the world
  • paclitaxel represents a breakthrough in the treatment of ovarian cancer, the overall 5-year survival rate of patients with stage III disease is still approximately 40%
  • Targeting cancer stem cells is an emerging concept in cancer therapy
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  • Ovarian cancer stem cells play an important role in chemoresistance and cancer recurrence
  • Furthermore, recent studies indicate that niclosamide exhibits anticancer effects against various human cancer cells by acting on multiple cell signaling pathways and inducing mitochondrial uncoupling [16–21]
  • This toxicity evaluation showed that oral nano-NI had no toxic effect on either group of mice in terms of weight, plasma albumin levels, and blood cell counts, and revealed no adverse effects on vital organ function in the rodents, which suggests that nano-NI is safe for animals
  • The nano-NI demonstrated significantly higher inhibitory effects on sphere formation than the original niclosamide did
  • the nano-NI formulation decreased the metabolic activity of ovarian cancer cells and caused a metabolic shift from oxidative phosphorylation to glycolysis
  • has low systemic bioavailability (~10%) when administered orally, which is beneficial for treating local parasitic infections of the intestines while minimizing systemic exposure
  • niclosamide inhibits tumor cell growth by interrupting multiple pathways (Wnt, Notch, STAT3, NF-κB, and mTORc1) and the generation of reactive oxygen species in several cancer cells
  • The current standard therapy for ovarian cancer includes taxanes and platinum-based chemotherapy after cytoreductive surgery. Among treated patients, nearly 70 to 80% will experience disease recurrence
  • Nathan Goodyear on 16 Apr 18
     
    nano-Niclosamide more effective than traditional Niclosamide in in vitro and in vivo ovarian cancer.
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Redox Regulation in Cancer Stem Cells - 0 views

www.hindawi.com/...750798 Cancer redox cancer stem cells CSC
shared by Nathan Goodyear on 04 Dec 18 - No Cached
  • Nathan Goodyear on 04 Dec 18
     
    Redox reactions in cancer stem cells
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BCL-2 inhibition targets oxidative phosphorylation and selectively eradicates quiescent... - 0 views

www.ncbi.nlm.nih.gov/...PMC3595363 CSC cancer stem cells leukemia oxidative phosphorylation cancer
shared by Nathan Goodyear on 28 Nov 18 - No Cached
  • Nathan Goodyear on 28 Nov 18
     
    Leukemia stem cells use oxidative phosphorylation metabolism via upregulation of bcl-2 gene.
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Aging | Doxycycline, Azithromycin and Vitamin C (DAV): A potent combination therapy for... - 0 views

www.aging-us.com/...text cancer stem cells cancer azithromycin IV vitamin C vitamin C doxycycline CSC
shared by Nathan Goodyear on 21 May 19 - No Cached
  • Nathan Goodyear on 21 May 19
     
    Triple attack on cancer stem cells. Doxy and Azithromycin with vitamin C found to significantly inhibit CSC mitochondrial activity.
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UCLA's Jonsson Comprehensive Cancer Center : In the News : Radiation Treatments Generat... - 0 views

www.cancer.ucla.edu/index.aspx radiation therapy treatment chemotherapy UCLA breast cancer stem cells
shared by Nathan Goodyear on 20 Mar 12 - No Cached
  • Nathan Goodyear on 20 Mar 12
     
    radiation therapy creates more aggressive cancer cells that are resistant to chemotherapy.  This study was done at UCLA on breast cancer cells.
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Radiation‐Induced Reprogramming of Breast Cancer Cells - Lagadec - 2012 - STE... - 0 views

stemcellsjournals.onlinelibrary.wiley.com/...stem.1058 CSC cancer radiation cancer stem cells
shared by Nathan Goodyear on 07 May 21 - No Cached
  • Nathan Goodyear on 07 May 21
     
    ionizing radiation increased the number of BCSCs in the overall breast cancer cell population
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Anti-helminth compound niclosamide downregulates Wnt Signaling and elicits antitumor re... - 0 views

www.ncbi.nlm.nih.gov/...PMC3117125 Niclosamide Wnt cancer colon cancer
shared by Nathan Goodyear on 21 Mar 18 - No Cached
  • Others have reported that niclosamide inhibits the NF-κB pathway in leukemia cell lines (26) or mTOR signaling in MCF-7 breast cancer cells
  • niclosamide enhances the anti-tumor effect of oxaliplatin
  • In the more rapidly growing tumor (HCT116), a dose of 200 mg/kg of body weight was needed to suppress the tumor growth
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  • however, 100 mg/kg of niclosamide could suppress the growth of the relatively slow-growing tumor (CRC039) to the same level
  • niclosamide was confirmed to inhibit the growth of human CRCs in NOD/SCID mice
  • niclosamide can inhibit Wnt pathway activation in CRC
  • The mechanism of action of the niclosamide in our studies is thought to be through internalization of Fzd1 and downregulation of Wnt pathway intermediaries
  • Recently, Jin et al. (26) reported that niclosamide inhibited the NF-κB pathway and increased reactive oxygen species levels to induce apoptosis in AML cells. In contrast, we did not observe any inhibitory effect of niclosamide on NF-κB signaling in our CRC model
  • oral administration of niclosamide does result in sufficient distribution of the drug into tumor tissue, to prove a prolonged inhibitory effect on Wnt/ß-catenin signaling, resulting in tumor growth inhibition
  • we required higher doses (100 ~ 200 mg/kg body weight) of niclosamide in order to demonstrate significant inhibition of tumor growth in NOD/SCID mice
  • niclosamide concentrations in tumor tissue showed good correlation with those in plasma, suggesting the efficient distribution of niclosamide from blood to tumor tissue
  • we observed downregulation of Dvl2 and ß-catenin cytosolic expression in niclosamide-treated tumor cells in vivo
  • One potential concern for the use of niclosamide as an anticancer therapy is the poor absorption of this drug
  • The Wnt signaling pathway, fundamental to embryonic tissue patterning, is also activated in stem-like cells
  • The canonical Wnt pathway is activated in approximately 80% of sporadic CRC primarily due to mutations in the APC gene
  • recent observations reveal that Wnt ligands or inhibitors may affect the growth and survival of colon cancer cells in spite of the presence of APC or CTNNB1 mutations
  • Nathan Goodyear on 21 Mar 18
     
    Niclosamide found to inhibit Wnt/B-catenin signaling pathway, and thus promotion of apoptosis, in colorectal cancer cells in Vivo study.  It was also found to augment chemotherapeutic.
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Oncotarget | NADH autofluorescence, a new metabolic biomarker for cancer stem cells: Id... - 0 views

www.impactjournals.com/...index.php vitamin C cancer alternative medicine natural
shared by Nathan Goodyear on 16 Mar 17 - No Cached
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  • Nathan Goodyear on 16 Mar 17
     
    Vitamin C outperforms experimental drug in stopping cancer stem cell activity.
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Reprogramming of non-genomic estrogen signaling by the stemness factor SOX2 enhances th... - 0 views

www.ncbi.nlm.nih.gov/...PMC3906332 ER-alpha genomic signaling ER alpha estrogen breast cancer non-genomic signaling
shared by Nathan Goodyear on 11 Mar 21 - No Cached
  • Nathan Goodyear on 11 Mar 21
     
    reprogramming of non-genomic estrogen signaling by the stemness factor SOX2 is a key molecular feature that determines the tumor-initiating capacity of breast cancer stem-like cellular states->non-genomic signaling upregulates ER-alpha and genomic signaling.
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A vascular niche and a VEGF-Nrp1 loop regulate the initiation and stemness of skin tumo... - 0 views

www.nature.com/...nature10525 cancer stem cells VEGF angiogenesis stem
shared by Nathan Goodyear on 23 Apr 21 - No Cached
  • Nathan Goodyear on 23 Apr 21
     
    Not specifically focused on CSC, but anti-angiogenic therapies via blockade of VEGF inhibit stem ness.
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Targeting colorectal cancer stem cells using curcumin and curcumin analogues: insights ... - 0 views

cancerci.biomedcentral.com/...s12935-015-0241-x curcumin tumeric cancer colorectal cancer colon cancer
shared by Nathan Goodyear on 11 Sep 17 - No Cached
  • Nathan Goodyear on 11 Sep 17
     
    curcumin effective in inhibition of cancer and cancer stem cell activity through increasing apoptotic genes, affecting cellular signaling, altering growth factor receptors, microRNAs, tumor spheroid formation, and epithelial-mesenchymal transition; and found to be helpful in increasing chemo sensitivity to chemo and radiotherapy.
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Hypercalcemia of malignancy and new treatment options - 0 views

www.ncbi.nlm.nih.gov/...PMC4675637 hypercalcemia calcium cancer
shared by Nathan Goodyear on 11 Sep 18 - No Cached
  • Hypercalcemia of malignancy occurs as the result of direct bone metastasis and via humoral mechanisms such as parathyroid hormone-related protein (PTHrP) or 1,25-dihydroxyvitamin D mediated pathways
  • ectopic secretion of parathyroid hormone (PTH) has been implicated
  • Hypercalcemia due to osteolytic bone lesions is common in multiple myeloma, leukemia, and breast cancer
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  • Humoral hypercalcemia is predominant in squamous cell, renal cell and ovarian cancers, and lymphomas are associated with 1,25-dihydroxyvitamin D mediated hypercalcemia
  • 20% of cases of hypercalcemia of malignancy and is frequently encountered in multiple myeloma, metastatic breast cancer, and to a lesser extent in leukemia and lymphoma
  • Physiologic bone turnover requires the complementary activity of osteoblasts – mesenchymal stem cell-derived bone-forming cells – and bone-resorbing cells of monocyte and macrophage lineage known as osteoclasts
  • In local osteolytic hypercalcemia, the RANKL/RANK interaction results in excessive osteoclast activation leading to enhanced bone resorption and thus hypercalcemia
  • In addition, osteoclast activation is also mediated by malignancy secreted cytokines, including interleukin-1, initially termed “osteoclast stimulating factor”
  • Macrophage inflammation protein 1-alpha (MIP 1-alpha)
  • hypercalcemia is through extra-renal 1,25-dihydroxyvitamin D (calcitriol) production
  • 1% of cases
  • increased production of 1,25-dihydroxyvitamin D occurs nearly exclusively in Hodgkin and non-Hodgkin lymphoma with case reports of the same in ovarian dysgerminoma
  • 1-α-hydroxylase in the kidney, a process regulated by PTH
  • in 1,25-dihydroxyvitamin D induced hypercalcemia, malignant cells likely recruit and induce adjacent macrophages to express 1-α-hydroxylase, converting endogenous calcidiol into calcitriol.31 Calcitriol then binds to receptors in the intestine leading to heightened enteric calcium reabsorption with resultant hypercalcemia
  • this mechanism of disease is best conceptualized as an absorptive form of hypercalcemia
  • Ectopic production of PTH by malignant cells has been described in a handful of cases involving cancer of the ovary and lung, as well as neuroendocrine tumors and sarcoma
  • primary hyperparathyroidism and malignancy comprising nearly 90% of cases of hypercalcemia
  • an initial panel consisting of PTH, PTHrP, phosphorus, 25-hydroxyvitamin D, and 1,25-dihydroxyvitamin D should be obtained
  • Lymphoma, a hypercalcemia due to 1,25-dihydroxyvitamin D mediated pathways, is implied by elevations in 1,25-dihydroxyvitamin D without concomitant elevations in 25-hydroxyvitamin D. In such cases, PTH is low and PTHrP undetectable
  • Treatment of hypercalcemia of malignancy is aimed at lowering the serum calcium concentration by targeting the underlying disease, specifically by inhibiting bone resorption, increasing urinary calcium excretion, and to a lesser extent by decreasing intestinal calcium absorption
  • mildly symptomatic disease
  • marked symptoms
  • hydration with isotonic fluid (if admitted), avoidance of thiazide diuretics, and a low-calcium diet
  • denosumab
  • Denosumab is an RANKL antibody that inhibits osteoclast maturation, activation, and function
  • Nathan Goodyear on 11 Sep 18
     
    hypercalcemia in cancer and treatments.
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Ascorbate regulates haematopoietic stem cell function and leukaemogenesis : Nature : Na... - 0 views

www.nature.com/...nature23876.html leukemia cancer vitamin c IV vitamin c Tet2
shared by Nathan Goodyear on 23 Oct 17 - No Cached
  • Nathan Goodyear on 23 Oct 17
     
    Low vitamin C levels accelerate the initiation of leukemia. High dose vitamin C found to accumulate and promote Tet2 activity in haematopoietic stem cells, thereby  decreasing initiation and progression of leukemia.
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Very small embryonic-like stem cells are involved in pancreatic regeneration and their ... - 0 views

stemcellres.biomedcentral.com/...s13287-015-0084-3 cancer stem cells VSEL
shared by Nathan Goodyear on 07 Jan 24 - No Cached
  • Nathan Goodyear on 07 Jan 24
     
    Dysfunctional VSEL triggers cancer? That is the proposal here.
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Antineoplastic Mechanisms of Niclosamide in Acute Myelogenous Leukemia Stem C... - 0 views

cancerres.aacrjournals.org/...2516 Niclosamide cancer leukemia NF-kappaB ROS TNF tumor necrosis factor
shared by Nathan Goodyear on 21 Mar 18 - No Cached
  • Here, we report on niclosamide as an antileukemic agent with two independent antineoplastic mechanisms: NF-κB pathway inactivation and ROS generation
  • In this report, we validated the inhibitory action of niclosamide against tumor necrosis factor (TNF)–induced NF-κB activation in AML cells and identified its mechanism, together with generation of reactive oxygen species (ROS), as being responsible for induced apoptosis of AML cells
  • NF-κB plays a critical role in inflammation, antiapoptotic responses, and carcinogenesis
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  • pharmacologic inhibition of NF-κB was effective in killing AML cells
  • High NF-κB expression is found in primitive human AML blast cells
  • niclosamide inhibited the TNF-induced NF-κB reporter activity in a dose- and time-dependent manner
  • niclosamide inhibiting TNF-induced IKK phosphorylation (Fig. 2A), niclosamide may exert its inhibitory effect at the TAK1 step
  • Pretreatment with niclosamide completely blocked the time- and dose-dependent TNFα-induced alteration of the NF-κB–DNA complex
  • niclosamide inhibited constitutively active NF-κB binding to DNA in U266 cells
  • niclosamide completely abolished the TNFα-induced phosphorylation of IKKα/β and IκBα
  • Accordingly, the TNFα-induced degradation of IκBα was abrogated by niclosamide
  • Nathan Goodyear on 21 Mar 18
     
    Old anti-parasitic medication, niclosamide, found to have anti-leukemic acitivty through inactivation of NF-kappaB and increase in ROS production in in Vitro and in Vivo study.
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